The art of managing metallic ions in food products has received much attention by the food industry. Metallic ions of iron, copper and zinc can be present in some food products with adverse effects on food integrity. If they are allowed to remain in some food products even in low concentrations, such metallic ions can greatly reduce shelf life of some fats, oils and other foods that are subject to spoiling and oxidization.
Chemical Sequestration of metallic ions: Sequestrants are chemicals that deactivate or stabilize these metallic ions by chemically typing up positively charged metal ions through chemical reactions to form stable, neutrally or negatively charged complexes that do not adversely affect integrity or quality of such food products. Sequestrants are also known as sequestering agents, stabilizers, chelators, chelating agents and metal scavengers. Sequestrants help to establish, maintain, and enhance integrity of many food products. From a food manufacturing viewpoint, sequestrants serve to stabilize or enhance numerous properties identified with wholesome food including color, flavor and texture. Usually, sequestrants chemically react with metallic ions to form complexes which, depending on stability of metal complexes, tend to alter properties and effects of metals in substrates. Many sequestrants employed in food production occur naturally in nature. They include as monocarboxylic acids gluconic and acetic acids which weakly sequester zinc ions; as hydroxycarboxylic acids citric and tartaric acids which strongly chelate zinc ions; as amino acids such as sweet tasting lysine, glycine, leucine, alanine, and valine; and various macromolecules such as porphyrins, peptides and proteins. Certain commercial sweeteners such as saccharin, sorbitol, mannitol and a constituent of aspartame, phenylalanine, have also been shown to bind with or sequester metals. For sequestration, chelation, to occur two general conditions must be met: (a) ligands must have proper steric and electronic configuration in relation to metal ions being complexed and (b) the surrounding milieu (pH, ionic strength, solubility, etc) must likewise be conductive to complex formation. That sequestration of metal ions is a desirable goal of food manufacturers is well known in the art.
Desirability of weak sequestration: However, desirability of strongly sequestering metal ions in all cases must be challenged in view of nature of some metal chelators relative to environments in which their use is intended. For example, use of zinc gluconate in lozenges and similar means has been described as a method for reducing duration of common cold symptoms (U.S. Pat. No. 4,503,070, Mar. 5, 1985 and its reissue U.S. Pat. No. Re 33,465). In such usage, zinc ions are only weakly bound by the gluconate moiety. The first stability constant of zinc gluconate is log K.sub.1 1.70. Thirty percent or more of zinc appears as positively charged zinc ions in acidic to neutral pHs, with remained being positively charged zinc gluconate. Such ions are available for those biochemical activities in oral and oral pharyngeal mucous membranes that result in a reduction in duration of common cold symptoms. Although the exact nature of biochemical activities of zinc ions in reducing duration of common cold symptoms remains to be determined, it is conclusive that zinc must be ionized. Published articles, "Reduction in Duration of Common Cold Symptoms by Zinc Gluconate Lozenges in a Double Blind Study", Antimicrobial Agents and Chemotherapy, 1984, 25(1), pp 20-24 by George A. Eby, et al and "Prophylaxis and Treatment of Rhinovirus Colds with Zinc Gluconate Lozenges", Journal of Antimicrobial Chemotherapy, 1987, 20(6), pp 893-901 by W. Al-Nakib, each used zinc gluconate either with no additional metal sequestrants added or with glycine added, and each showed a marked reduction in duration of common cold symptoms from positively charged zinc ions.
Adverse effects of sequestration: Conversely, in a similar study "Two Randomized Controlled Trials of Zinc Gluconate Lozenge Therapy of Experimentally Induced Rhinovirus Colds", Antimicrobial Agents and Chemotherapy, 1987 31(8) pp 1183-1187, by Barry M. Farr et al, citric acid, a strong zinc chelator, was used in lozenges in extramolar amounts sufficient to eliminate taste of zinc, resulting in no reduction in duration of common colds. The first stability constant of citric acid for zinc ions is generally accepted to be log K.sub.1 4.5. In oral use in lozenge form, zinc gluconate rapidly ionizes; as does zinc combined with other ligands having low stability constants, or other ligands that produce positively charged zinc ions such as glycine. It is known in the art that if such occurs in the presence of sufficient amount of a chelator having a high stability constants for zinc ions such as equimolar (or greater) citric acid, a new, vastly stronger equilibrium may occur. Such equilibrium may result in neutrally or negatively charged compounds having little or no bioavailability at salivary pH and normal oral tissue pH. In the case of lozenges containing zinc gluconate with extramolar citric acid, soluble zinc complexes were shown to be tasteless and were proposed to be sufficiently biologically available to be effective in reducing duration of common colds. However, with addition of extramolar citric acid, there occurs in saliva such powerful binding of zinc ions that negatively charged zinc species predominate. A complete loss of positively charged zinc ions in saliva and in oral tissues occurs. There is no metallic taste. No localized activity occurs, and no reduction in common cold duration occurs.
Stability of compositions containing zinc: In addition to the requirement that all ingredients in said compositions not adversely affect efficacy, ingredients must not adversely affect composition taste. They must be thermally, chemically and flavor stable under all normal conditions over long periods of time. This inventor conducted year-long laboratory tests of taste stability of hundreds of originally pleasant tasting, flavor masked zinc compositions. Various flavor masks, including glycine and anethole were tested. Glycine treated zinc gluconate under U.S. Pat. No. 4,684,528 was provided by the inventor, John C. Godfrey. Anethole has been discovered to be an aromatic flavor mask and aftertaste mask for all soluble and ionizable zinc compounds and is disclosed and claimed by George A. Eby III in U.S. patent application Ser. No. 182,983 dated Apr. 18, 1988, now U.S. Pat. No. 5,002,970, issued 3-26, 1991. All known sweet tablet bases such as sugar, dextrose, lactose, fructose, mannitol, sorbitol, xylitol and many other commercial products specifically designed for pharmaceutical tablets were tested with zinc compounds and flavor masks. Compositions kept in a closed un-air conditioned room were exposed to summer-time temperatures reaching 45 to 55 C. degrees. Glycine flavor masked zinc gluconate compositions in Mendell's Sugartab.RTM. turned brown, apparently from high summer temperatures. Anethole (plated onto silica gel) flavor-asked zinc gluconate lozenge compositions of Sugartab.RTM. lost most of their flavoring and became bitter with the highly objectionable aftertaste typically found with zinc gluconate and sucrose. Zinc gluconate with or without glycine did not adversely react or become bitter only in fructose lozenges. Flavors usually evaporated, suggesting that plating flavors on silica gel is inadequate for a flavor stable product, suggesting a need for spray dried flavors or flavor oil incorporated within cyclodextrins. Zinc acetate lozenges which originally contained anethole and other flavors, had no zinc aftertaste even if anethole had evaporated. Zinc acetate lozenges without anethole were not made. Said changes indicate that unexpected, undesired reactions occurred which are destructive to compositions. Such changes may inhibit commercial utility and preclude wide spread marketability of said compositions unless satisfactory solutions can be developed.
Other experiments: U.S. Pat. No. 4,684,528 shows that candy lozenges and various other oral compositions containing various zinc compounds, including zinc gluconate and zinc acetate, can be flavor masked with glycine and certain other amino acids. Amino acids found effective as a flavor mask and aftertaste mask are glycine, L-alanine, D,L-alanine, L-2-aminobutyric acid, D,L-2-aminobutyric acid, L-valine, D,L-valine, L-isovaline, D,L-isovaline, L-leucine, D,L-leucine, D-isoleucine, D,L-isoleucine, L-lycine, and D,L-lycine when molar ratio of said amino acids to zinc is from about 2 to 20. Importantly, said patent reveals that a zinc acetate formulation of hard candy without glycine had a sharp, undesirable taste and an unpleasant aftertaste.
The current need: In as much as there is an important need to develop thermally, chemically and flavor stable zinc lozenges and other means having a pleasant taste to introduce zinc ions into oral and oral pharyngeal mucous membranes primarily for treatment of common colds and nutritional supplementation; and in as much as serious mistakes taken from the prior art of taste management of zinc and other metallic ions have been made, particularly in the invention of thermally, chemically and flavor stable zinc lozenges for treating common colds; it is apparent that errors of the prior art must receive attention. A new way of eliminating objectionable taste and aftertaste of ionizable zinc compounds is needed using stable lozenge ingredients and new technology.